PSMA-Targeted Activated Myeloid Cells as a Novel Prostate Cancer Immunotherapy
Abstract
Adoptive transfer of immature myeloid cells lacking NF-kB p50 (p50-IMC) slows growth of prostate cancer (PrCa) tumors, and the large majority of human PrCa expresses PSMA. We hypothesize that co-administering PSMA antibody (Ab) or expressing a PSMA-targeting chimeric antigen receptor (CAR) on p50-IMC will direct p50-IMC to PrCa and enable phagocytosis and Ag presentation to T cells, increasing efficacy. We obtained anti-human PSMA Ab from a hybridoma, constructed a PSMA.CAR,and demonstrated their binding to human PSMA (hPSMA), but not mouse PSMA. We expressed hPSMA in two murine PrCalines (Myc-CaP and TRAMP-C1); these lines form tumors in immune-deficient NSG mice that retain hPSMA but lose hPSMAin syngeneic mice, indicating immune-rejection. PSMA.CAR increased p50-IMC Myc-CaP/hPSMA phagocytosis. EGFR andGD2 are expressed on a subset of aggressive PrCa tumors. We also constructed a CAR recognizing human EGFR (hEGFR)and developed Myc-CaP and TRAMP-C1 lines expressing hEGFR. These lines retain hEGFR in NSG but again lose hEGFRin syngeneic mice. TRAMP-C1 cells express GD2 retain this ganglioside in syngeneic mice and are slowed by p50-IMC. We are assessing whether hPSMA or GD2 Abs or CARs increase murine or human p50-IMC PrCa tumor localization and efficacy in syngeneic or NSG mice, and are developing transgenic mice expressing hPSMA that will tolerate Myc-CaP/hPSMA cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1191067
Entities
People
- Alan D Friedman
Organizations
- Johns Hopkins University